Cheryl Allen, BS Pharm, MBA: Methotrexate is the cornerstone treatment for rheumatoid arthritis. The mechanism of action for methotrexate is acting at the molecular level, so it acts on the B cells, the T cells, and the cytokines to reduce the amount of inflammatory substance in the synovial fluids. Considerations of drug interactions with methotrexate need to consider alcohol administration along with methotrexate due to liver toxicities.
The side effects of methotrexate are most commonly GI in nature—nausea, vomiting, diarrhea. We could also see some mouth ulcers. There could be CNS side effects—dizziness and headaches—and there’s also a phenomenon that could happen in some patients. It’s called a methotrexate fog, and this generally happens within 24 hours of the weekly methotrexate dose. The majority of these side effects can be alleviated by providing the patient with folic acid supplementation. So, it would be 1 mg a day or 5 mg a week. Most patients generally go for the weekly dose because their methotrexate is dosed once a week, so it’s more convenient. For the mouth ulcers, we can treat mouth ulcers with lidocaine—a swish and spit. So, these side effects can be managed.
Some patients may find that they have fewer side effects with the subcutaneously administered methotrexate. This would have fewer of the systemic effects, so we may find that subcutaneous administration is warranted when patients are having too many side effects with the oral dose. Subcutaneous methotrexate does generally require prior authorization. This is interesting, we think, because the guidelines are silent to the dosage form. So, we do find that with the branded products for subcutaneous administration, we require prior authorization. Now, generally, those prior authorizations would include side effects that the patient can’t tolerate on the oral forms and the movement over to the subcutaneous forms—to clarify, that would be the branded products that are subcutaneous that we’re seeing prior authorization requests for.
What we find is the majority of patients who are on subcutaneous methotrexate started on oral methotrexate. Now, in the studies, we can find that there is an advantage to starting patients on injectable methotrexate. It would help if we had the guidelines that would differentiate between oral or subcutaneous administration of methotrexate, but today we don’t have that, so we would look for some education around patients who could benefit from subcutaneous-administered methotrexate.
Many of the patients we see who are on subcutaneous methotrexate are patients who either have caregiver issues with administering the methotrexate or have rheumatoid arthritis where it affects the joints of the hands and it may be difficult for them to administer a subcutaneous form. So, we see those patients moving over to a branded subcutaneous product that may have some type of delivery advantage, such as an autoinjector. This can help those patients where they have difficulty in administration.
Safety and efficacy for subcutaneous-administered methotrexate is about the same as orally administered methotrexate. And as far as adherence to the medication, what we find is the more educated the patient is—whether it’s around the injection of the product or taking the product by mouth—the more educated the patient is on the value of the therapy and the more compliant they are to therapy.
Adherence to subcutaneous methotrexate is very important. One of the things we want to make sure of is that the patient fully understands the value of the treatment and the value of that weekly injection. So, the role of the specialty pharmacist is to reaffirm the injection-site training, make sure the patient fully understands how do to this injection-site training, and—as far as compliance—that they understand the value of that weekly injection in helping to control their disease. As the patient receives the benefits of methotrexate, their symptomatology is going to become better. And we have to make sure the patient understands that they need to continue that weekly injection in order to control those symptoms.
As a specialty pharmacy, we work with the prescriber and the payer to help that patient gain access to the branded products for subcutaneous methotrexate administration. Now, many times, we need to work with the prescriber to look at the patient’s history—what they tried, what failed. Today methotrexate is available in a vial, and we can have the patient administer that by putting the product into syringes and self-administering. At times, this procedure doesn’t work for some patients. The rheumatoid arthritis in their hands makes it difficult for them to use the vial and syringe, and, in this case, it would be very appropriate for that patient to move on to some of the branded products that have addressed this issue. So, some of the branded products have autoinjectors that are very easy for these patients to use, and it helps them to stay compliant to the medication and also self-sufficient.
The specialty pharmacy is working in between the prescriber to look at what the patient has tried and failed and then filling out the appropriate prior authorization paperwork necessary to prove that the patient has tried and failed these products, really to provide some more information, so that we can get access. So, from the payer’s perspective, the payer wants their patient to be compliant to therapy. They know that they have a patient who was diagnosed with rheumatoid arthritis. They want to make sure that they’re getting the right drug to the patient. We don’t see huge barriers when we’re trying to get these branded products approved for patients, but we do need the appropriate documentation.
Working with the payers to show how patients are doing on treatment is really an overall rheumatoid arthritis profile approach. The payer will get reports on the different ways that the patients are administering. Patients are administering these products subcutaneously, orally, or through IV. And within those subcutaneous administrations, the payer will look at durability on those patients and then see how those patients are doing with other resources that they’re using. So, some of the very interesting ways to look at return on investment is really to look at how compliant the patients are to drug therapy and then compare that with the overall utilization of resource from a payer perspective. And I think this is the way that we can look at patients choosing methotrexate as being very cost-efficient for the payers.
For patients who are on methotrexate therapy, it’s very important to make sure that the prescriber is kept in the loop so there’s an entire continuum of care concept that really provides that information back. Typically, the prescribers get alerted when we have adherence issues or when patients have issues with administration of their medications. So, really it would be in this area that the patient would notify the pharmacy if they’re having difficulties in administration. It may be some opportunity to alert the physicians that there may be an opportunity for a better way to subcutaneously administer these products for some patients.